NCT04797260

Brief Summary

This study is a prospective, non-randomized, open-label, two-centre phase I/II intervention study designed to treat children up to 24 months of age with RAG1-deficient SCID with an indication for allogeneic hematopoietic stem cell transplantation but lacking an HLA-matched donor. The study involves infusion of autologous CD34+ cells transduced with the pCCL.MND.coRAG1.wpre lentiviral vector (hereafter called RAG1 LV CD34+ cells) in five patients with RAG1-deficient SCID.

Trial Health

83
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for not_applicable

Timeline
45mo left

Started Jul 2021

Longer than P75 for not_applicable

Geographic Reach
7 countries

7 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress57%
Jul 2021Dec 2029

First Submitted

Initial submission to the registry

March 11, 2021

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 15, 2021

Completed
4 months until next milestone

Study Start

First participant enrolled

July 23, 2021

Completed
8.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2029

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2029

Last Updated

April 18, 2024

Status Verified

April 1, 2024

Enrollment Period

8.4 years

First QC Date

March 11, 2021

Last Update Submit

April 17, 2024

Conditions

Severe Combined Immunodeficiency Due to RAG1 Deficiency

Keywords

SCIDRAG1Gene Therapy

Outcome Measures

Primary Outcomes (2)

  • Feasibility of successful generation of RAG1 LV CD34+ cells

    IMP (RAG1 LV CD34+ cells) that meets the release criteria as defined in the IMPD.

    2 years

  • Safety of RAG1 lentiviral gene therapy

    Overall survival and event-free survival (EFS) after infusion of the IMP with events

    2 years

Secondary Outcomes (8)

  • T cell reconstitution

    1 year

  • Thymic function

    1 year

  • T and B cell receptor repertoire

    1 year

  • Immunoglobulin dependence

    2 years

  • Persistence of gene marking

    1 year

  • +3 more secondary outcomes

Study Arms (1)

Gene therapy

EXPERIMENTAL

In this arm, 10 patients will be included for gene therarpy

Genetic: Gene therapy

Interventions

Gene therapyGENETIC

Patients will be infused with autologous CD34+ cells transduced with the pCCL.MND.coRAG1.wpre lentiviral vector (RAG1 LV CD34+ cells).

Gene therapy

Eligibility Criteria

Age8 Weeks - 24 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • RAG1-deficient SCID as confirmed by genetic analysis
  • Peripheral blood T cells \< 300/μL and/or naïve T cells \< 1/μL
  • Age \< 2 years
  • Age at least 8 weeks by the time of busulfan and fludarabine administration
  • Lack of an available HLA-matched donor (HLA-identical sibling or 10/10 (A, B, C, DR, DQ) allele-matched (un)related donor)
  • Signed informed consent (parental or guardian)
  • Able to return to the study centre for follow-up (per protocol) during the 2-year study and the 15-year long-term off study review

You may not qualify if:

  • Availability of an HLA-matched donor (HLA-identical sibling or 10/10 (A, B, C, DR, DQ) allele-matched (un)related donor)
  • RAG1 deficiency with peripheral blood T cells \> 300/μL and/or naïve T cells \> 1/μL
  • Omenn syndrome
  • Previous allogeneic HSCT
  • Significant organ dysfunction/co-morbidity (including but not limited to the ones listed below):
  • Mechanical ventilation
  • Shortening fraction on echocardiogram \<25%
  • Renal failure defined as dialysis dependence
  • Uncontrolled seizure disorder
  • Any other condition that the investigator considers is a contraindication to collection and/or infusion of trans-duced cells for that individual or indicate patient's inability to follow the protocol, for example contraindication f to busulfan, major congenital abnormalities, ineligible to receive anaesthesia, or documented refusal or inability of the family to return for scheduled visits.
  • Human immunodeficiency virus (HIV) infection or Human T-cell Leukemia Virus (HTLV) infection

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

The Royal Childrens Hospital

Melbourne, 3052, Australia

NOT YET RECRUITING

Ospedale Pediatrico Bambino Gesù

Roma, Italy

NOT YET RECRUITING

Leiden University Medical Center

Leiden, 2300RC, Netherlands

RECRUITING

Wroclaw Medical University

Wroclaw, 50-556, Poland

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Erciyes Üniversitesi TIP Fakültesi

Kayseri, Turkey (Türkiye)

RECRUITING

University College London Great Ormond Street

London, United Kingdom

NOT YET RECRUITING

Related Publications (1)

  • Garcia-Perez L, van Eggermond M, van Roon L, Vloemans SA, Cordes M, Schambach A, Rothe M, Berghuis D, Lagresle-Peyrou C, Cavazzana M, Zhang F, Thrasher AJ, Salvatori D, Meij P, Villa A, Van Dongen JJM, Zwaginga JJ, van der Burg M, Gaspar HB, Lankester A, Staal FJT, Pike-Overzet K. Successful Preclinical Development of Gene Therapy for Recombinase-Activating Gene-1-Deficient SCID. Mol Ther Methods Clin Dev. 2020 Mar 31;17:666-682. doi: 10.1016/j.omtm.2020.03.016. eCollection 2020 Jun 12.

    PMID: 32322605RESULT

MeSH Terms

Interventions

Genetic Therapy

Intervention Hierarchy (Ancestors)

Biological TherapyTherapeuticsGenetic EngineeringGenetic TechniquesInvestigative Techniques

Study Officials

  • Arjan C Lankester, Prof.dr.

    Leiden University Medical Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Arjan C Lankester, Prof. Dr.

CONTACT

0031715264871A.Lankester@lumc.nl

Estefania Laney, MSc.

CONTACT

0031715296242e.laney@lumc.nl

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: CD34+ HSC from patient will be obtained by leukapheresis or from bone marrow. After purification, CD34+ cells will be transduced with the SIN-LV-RAG1 vector. Transduced cells will be cryopreserved. Upon confirmation of successful transduction and meeting the release criteria as RAG1 LV CD34+ cells, patient conditioning will be allowed to start. After patient conditioning, cryopreserved RAG1 LV CD34+ cells will be thawed and administered to the patient. In case of failure of hematopoietic reconstitution after infusion of the RAG1 LV CD34+ cells the autologous backup graft will be infused to rescue the patient from aplasia. In addition, a conventional allogeneic HSCT procedure will be scheduled. Patients included in this study will be monitored on protocol during the first two years after infusion of the RAG1 LV CD34+ cells as per study protocol. Follow up as part of the routine clinical care for post-transplant patients will be annual after this, for at least 15 years after infusion.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

March 11, 2021

First Posted

March 15, 2021

Study Start

July 23, 2021

Primary Completion (Estimated)

December 31, 2029

Study Completion (Estimated)

December 31, 2029

Last Updated

April 18, 2024

Record last verified: 2024-04

Data Sharing

IPD Sharing
Will not share

Locations

TU(1)AU(1)NL(1)PL(1)IT(1)GB(1)ES(1)